1. Field of the Invention
The present invention relates generally to the field of peptides reactive with antibodies formed against human papillomavirus (HPV). Some have termed this type of peptide as antigenic or immunoreactive. More particularly, the invention relates to peptides isolated, purified or derived from the early coding region of the E2, E6, and E7 oncoproteins of HPV and method for use for the detection and/or diagnosis of HPV associated epithelial cell abnormalities, precancerous conditions and cancers via an immunoassay.
2. The Background Art
The human papillomaviruses (HPV), named because certain types induce warts or papillomas, cause virtually all cervical cancers (Nobbenhuis et al., “Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study,” The Lancet, 354:20-25, 1999; Cuzick et al., “A systematic review of the role of human papilloma virus (HPV) testing within a cervical screening programme: summary and conclusions,” British Journal of Cancer, 83:561-565,2000). These encompass not only squamous cell carcinomas (Nobbenhuis et al., 1999) but also adenocarcinomas (Pirog et al., “Prevalence of human papillomavirus DNA in different histological subtypes of cervical adenocarcinoma,” American Journal of Pathology, 157:1055-1062, 2000). These viruses are also strongly associated with vulvar and vaginal carcinomas (Frisch et al., “Human papillomavirus-associated carcinomas in Hawaii and the mainland US,” Cancer 88:1464-1469, 2000; Sugase et al., “Distinct manifestations of human papillomaviruses in the vagina,” International Journal of Cancer, 72:412-415, 1997), as well as cancers of the anus (Frisch et al., 2000) and penis (Gregoire et al., “Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma,” Journal of the National Cancer Institute, 87:1705-1709, 1995).
Moreover, HPV may be responsible for certain carcinomas in the head and neck region (Mellin et al., “Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival,” International Journal of Cancer, 89:300-304, 2000; Zumbach et al., “Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in patients with head-and-neck squamous-cell carcinoma,” International Journal of Cancer, 85:815-818, 2000), seem associated with the more deadly melanomas (Dreau et al., “Human papillomavirus in melanoma biopsy specimens and its relations to melanoma progression,” Annals of Surgery, 231:664-671, 2000), and could play a role in lung carcinomas (Soini et al., “Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma,” Thorax 51:887-893, 1996) and perhaps other cancers.
Cervical cancer is the second most common cancer among women worldwide. Each year about 450,000 women worldwide are diagnosed with cervical cancer, and nearly 300,000 women die of this disease. Since the advent of organized cervical cancer screening by cytology fifty (50) years ago, the mortality rate of cervical cancer has dramatically decreased in developed countries. In fact, cervical cancer may be considered preventable. In this regard, an important key to prevention is the timely identification and management of precancerous lesions and otherwise early cancers through accessible and affordable screening programs and methodologies.
At present, about twelve percent (12%) of female cancers worldwide are due to HPV infections of the cervix. There is consensus among the medical community that oncogenic HPV detection would be an effective way to identify cancer victims or those at high risk for the disease. Notably, HPV detection would facilitate earlier detection of cancer or cellular abnormalities suggesting cancer at a point in time when the cancer or cellular abnormalities exists at a more readily curable stage.
A primary methodology for public health screening for cervical cancer has been the Papanicolaou (Pap) smear. For a variety of reasons, the Papanicolaou smear is less than an ideal screening test. Drawbacks may include difficulty of obtaining samples, high rate of false negatives (up to twenty percent (20%)), and requirements for specialized labs staffed by highly trained personnel. Nucleic acid screening methods have been developed by those skilled in the art, but are not ideal primarily due to their high cost and like requirement for highly trained personnel. Another assay developed by those skilled in the art involves the so-called “DNA Hybrid Capture.” This method, however, tends to suffer from high cost and sampling difficulties, thus making it somewhat disadvantageous as an ideal screening test.
Recently, those skilled in the art have developed methodologies for examining the utility of HPV for diagnostic purposes. More particularly, IgA, IgG and IgM antibodies raised against HPV have been used in the detection of infection with HPV and for diagnosing carcinoma or pre-stages thereof. Using these prior art techniques, immunoreactive peptides isolated from HPV have been defined to have an epitope which is reactive with human sera. The prior art does not, however, disclose the peptides of the present invention, nor teach that multiple combinations of antibody-epitope complexes could be contemplated to produce diagnostic assays with improved sensitivity and/or specificity.
Such prior art methods for cancer screening, are limited by their cost, sampling procedures, accuracy, equipment and personnel requirements. Therefore, and as readily appreciated by those skilled in the art, low cost, simple, sensitive and specific assays that can be performed on readily obtainable bodily samples would be a significant advancement in the art. Such assays are disclosed and claimed herein.